Families with inherited cancer syndromes have provided important information with implications for the more common sporadic forms of malignancies in the general population. The identification of germ line mutations in tumor suppressor genes in some rare families with unusual cancer syndromes have provided important clues to molecular alterations involved in diverse tumor types. The growing list of tumor suppressor genes, and the increasing ability to identify mutations therein, increase the likelihood that molecular markers of susceptibility to cancer will soon have a significant impact on medical care. Full exploitation of these capabilities are likely to have substantial ramifications for individuals and society. The identification of germ line mutations in the p53 tumor suppressor gene in members of families with the Li-Fraumeni cancer syndrome and its variants provides a defined population in which to approach many issues of importance to predictive testing for cancer genes. In this pilot project, we will invite adult members of classic and variant Li-Fraumeni families at 50% risk of carrying an altered p53 gene to participate in a program in which they could be made aware of their p53 status. We will assess the expectations and motivations of at-risk adults and their partners for participation in a program of predictive testing. We will explore their psychological preparedness to participate, and, after disclosure of results, will evaluate the impact of the knowledge of their p53 status on their psychological well-being and family relationships. We will assess their understanding of genetic information, and will provide extensive genetic counseling regarding relevant choices and their implications throughout the process. We will explore with them the readiness of subjects who are parents and prospective parents to enter their at-risk children into a predictive testing program were it to exist, and what features of such a program might be important to families. We will also assess the receptiveness of the population to advice regarding disease surveillance and risk avoidance. We will conduct this program with full cognizance of the complex ethical and social issues which are inextricable from this work. This project is submitted to the attention of the Ethical Legal and Social Implications program of the Human Genome Initiative.